van der Weyden Louise, Del Castillo Velasco-Herrera Martin, Cheema Saamin, Wong Kim, Boccacino Jacqueline M, Vermes Ian, Offord Victoria, Droop Alastair, Jones David R A, Anderson Elizabeth, Hardy Claire, de Saint Aubain Nicolas, Ferguson Peter M, Mogler Carolin, Rajan Neil, Frew Derek, Harms Paul W, Billings Steven D, Schatton Désirée, Segarra-Mondejar Marc, Arends Mark J, Ferreira Ingrid, Brenn Thomas, Frezza Christian, Adams David J
Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, Cambridge, UK.
Br J Dermatol. 2025 Feb 18;192(3):551-553. doi: 10.1093/bjd/ljae432.
To comprehensively explore the mutational landscape of cutaneous leiomyoma (cLM) and identify candidate driver events, we performed a retrospective, multi-institutional, whole-exome sequencing and RNA sequencing study. We confirmed that a large proportion of patients with cLM have germline variants and additionally showed that somatic alteration of also drives cLM, with biallelic inactivation of being a frequent event. Treatment of -proficient and -deficient cell lines with the purine antagonist and chemotherapeutic agent, mercaptopurine, significantly decreased growth/colony formation; however, the addition of nucleosides was able to rescue only the -proficient cells, suggesting that purine metabolism is a targetable vulnerability for -deficient cLMs.
为了全面探索皮肤平滑肌瘤（cLM）的突变图谱并确定候选驱动事件，我们进行了一项回顾性、多机构的全外显子组测序和RNA测序研究。我们证实，很大一部分cLM患者存在种系变异，此外还表明，[此处原文有缺失信息]的体细胞改变也驱动cLM，双等位基因失活是常见事件。用嘌呤拮抗剂和化疗药物巯嘌呤处理[此处原文有缺失信息] proficient和[此处原文有缺失信息] deficient细胞系，显著降低了生长/集落形成；然而，添加核苷只能挽救[此处原文有缺失信息] proficient细胞，这表明嘌呤代谢是[此处原文有缺失信息] deficient cLMs的一个可靶向的脆弱点。
